title: Kinetic and mechanistic studies on reactions of diruthenium(II,III) with biologically relevant reducing agents.
abstract: Diruthenium(ii,iii)-tetracarboxylates have shown promising anticancer properties as metallotherapeutics. On the basis of the role that bio-reducing agents may play on the mode of action of ruthenium-based anticancer drugs, we performed detailed kinetic studies on the reaction of ascorbic acid and glutathione with the [Ru2(RCOO)4](+) paddlewheel framework by using the non-drug, diaqua complex ion [Ru2(CH3COO)4(H2O)2](+). In the presence of the reducing agents, the diaqua-Ru2 species first undergo a ligand substitution reaction by which the axially-coordinated water is displaced by the reducing agent. In both cases, this reaction is followed by an intra-molecular electron transfer process during which the metal-metal center is reduced from Ru2(5+) to Ru2(4+) and the reducing agent is oxidized. Product analyses were performed with the application of ESI-MS and (1)H-NMR techniques. Rate and activation parameters are reported for the different reaction steps.
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes, 748, B2 T, CEP 05508-000, São Paulo, SP, Brazil. deosilva@iq.usp.br.
authors.forename: Rodrigo Luis Silva Ribeiro
authors.initials: RL
authors.lastname: Santos
authors.forename: Rudi
authors.initials: R
authors.lastname: van Eldik
authors.forename: Denise
authors.initials: D
authors.lastname: de Oliveira Silva
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism*; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D019163:Reducing Agents / Q000378:metabolism*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D019163:Reducing Agents; D012428:Ruthenium; D005978:Glutathione; D001205:Ascorbic Acid